Three types of opioid receptors, μ (mu), δ (delta) and κ (kappa) have been identified. These receptors may be indicated with combinations of OP (abbreviation for Opioid Peptides) and numeric subscripts as suggested by the International Union of Pharmacology (IUPHAR). Namely, OP1, OP2 and OP3 respectively correspond to δ-, κ- and μ-receptors. It has been found out that they belong to G-protein-coupled receptors and are distributed in the central nervous system (CNS), peripheries and organs in a mammal. As ligands for the receptors, endogenous and synthetic opioids are known. It is believed that an endogenous opioid peptide produces its effects through an interaction with the major classes of opioid receptors. For example, endorphins have been purified as endogenous opioid peptides and bind to both δ- and μ-receptors. Morphine is a well-known non-peptide opioid analgesic and has binding affinity mainly for the μ-receptor. Opiates have been widely used as pharmacological agents, but drugs such as morphine and heroin induce some side effects such as drug addiction and euphoria.
Meunier et al. reported isolation of a seventeen-amino-acid-long peptide from rat brain as an endogenous ligand for an orphan opioid receptor (Nature, Vol. 337, pp. 532-535, Oct. 12, 1995), and said receptor is now known as “opioid receptor-like 1 (abbreviated as ORL-1 receptor)”. In the same report, the endogenous opioid ligand has been introduced as agonist for the ORL-1 receptor and named as “nociceptine (abbreviated as NC)”. Also, the same ligand was named as “orphanin FQ (abbreviated as OFQ or oFQ)” by Reinscheid et al. (Science, Vol. 270, pp. 792-794, 1995). This receptor may be indicated as OP4 in line with a recommendation by IUPHAR in 1998 (British Journal of Pharmacology, Vol. 129, pp. 1261-1283, 2000).
International Patent Application Number (WO) 9429309 discloses a variety of spiro-substituted azacycle compounds, which are Neurokinin antagonists useful in the treatment of pain.
Also, International Patent Application Number (WO) 9825605 discloses a variety of spiro-substituted azacycle compounds, which are Chemokine receptor activity modulator antagonists.
Further, International Patent Application Number (WO) 0226714 discloses a variety of spiropiperidino compounds which show a binding affinity to a Nociceptin receptor.
Yet further, International Patent Application Number (WO) 03064425 discloses a variety of spiropiperidino compounds, which are ORL1 antagonists, for example, compound (i) below:

Compound (i) shows a potent activity in the dofetilide binding assay.
There is a need to provide new ORL1 antagonists that are good drug candidates. In particular, preferred compounds should bind potently to the ORL1 receptor and show functional activity as antagonists whilst showing little affinity for other receptors. They should be well absorbed from the gastrointestinal tract, be metabolically stable and possess favorable pharmacokinetic properties and less drug-drug interaction. They should be non-toxic and demonstrate few side-effects. Furthermore, the ideal drug candidate will exist in a physical form that is stable, non-hygroscopic and easily formulated.
In particular, it would be desirable to provide an ORL1 antagonist with reduced inhibitory activity at HERG potassium channel.